Riverside Research and the University of Hawaii and its affiliated Kuakini Medical Center propose to assess the feasibility of applying quantitative photoacoustic (QPA) methods to detection of metastases in lymph nodes in conjunction with its funded studies of novel quantitative ultrasound (QUS) methods for discriminating between cancer-containing and cancer-free lymph nodes of cancer patients. Detection of metastatic cancer in lymph nodes is crucial for accurate staging, prognosis, and treatment planning. Our goal is to reduce markedly the failure of existing methods to detect metastases in 25% to 30% of dissected nodes and 50% in nodes with micrometastases. To achieve our goal, we propose to develop QPA methods used alone or in combination with high-frequency QUS to identify regions of nodes that warrant careful histologic examination. We already have made exciting progress toward this goal by developing a highly sensitive and specific, purely ultrasonic method of imaging metastatic disease in lymph nodes with fine spatial resolution. Our ultrasonic results show a remarkable ability to detect cancer in dissected lymph nodes for a broad range of cancer types, and they promise a reliable means of guiding pathologists to cancer-containing regions of dissected lymph nodes. The ability of our ultrasonic methods to pinpoint metastatic cancer potentially can reduce or eliminate the occurrence of unacceptable false-negative determinations drastically when nodes actually contain micrometastatic disease. These findings provide encouragement that our proposed studies combining novel QPA methods with our QUS methods may be able to achieve simultaneous sensitivity and specificity values approaching 100%. Therefore, we plan to acquire QPA-signal data in conjunction with acquisition of QUS- signal data, and to use the results of analyses of these data in a multifeature approach to classification of lymph-node tissue as cancerous or non-cancerous. If the proposed studies establish the feasibility of using QPA alone or in combination with QUS, then we will propose to undertake validation studies that, if successful, can provide a foundation for future development of a prototype node-evaluation instrument for use in the pathology laboratory. In the more-distant future, we also will investigate application of these QPA and QUS techniques at lower ultrasound frequencies for use in the examination or operating room to identify nodes that warrant biopsy or dissection. In conclusion, this project can benefit lymph-node evaluations for staging, prognosis, and treatment planning of all types of cancers, e.g., breast, colorectal, gastric, pancreatic, lung, thyroid, prostate, etc., as well as sentinel-node dissection procedures, e.g., for breast cancer. The methods we are developing clearly can have a significant beneficial impact on in situ evaluations of lymph nodes examined prior to or during surgery, intra-operative evaluations of regional nodes including sentinel-nodes, and post- operative evaluations of dissected nodes. These methods also may be of use in evaluations of non-cancerous diseases such as cardiac disease, musculoskeletal disease, etc.